Abstract: Molecular dynamics simulations were employed to comparatively investigate the interaction mechanisms of the antimicrobial peptides Magainin and Indolicidin with the cell membranes of Gram-negative and Gram-positive bacteria, respectively. Structural changes, adsorption process, membrane perturbations, and peptide-membrane interactions of both peptides were systematically analyzed. The results demonstrate that Magainin, which exhibits an unstable helical structure in an aqueous environment, forms a stable helix upon binding to membranes. Moreover, it shows stronger binding ability and more significant disruption on the membrane of Gram-negative bacteria, indicating its higher selectivity for this type of bacteria. In contrast, Indolicidin maintains a flexible random coil structure, enabling rapid adsorption and stable binding to the membrane surface primarily through synergistic electrostatic attraction and hydrophobic interactions. However, it causes relatively minor perturbation to both types of bacterial membranes. This comparative study provides a theoretical basis for understanding the selectivity of Magainin for Gram-negative bacteria and the broad-spectrum activity of Indolicidin.

Key words: Magainin, Indolicidin, Gram-negative bacterial membrane, Gram-positive bacterial membrane